The importance of bone health in end-stage renal disease: out of the frying pan, into the fire?

Abstract

In the early stages of renal failure, hyperparathyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol. As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy (ROD). Over the past decade, the pattern of ROD seen in patients with chronic kidney disease (CKD) has changed. Previously, the majority of patients had mixed uraemic osteodystrophy or aluminium-related osteomalacia. The decreased use of aluminium-based phosphate binders, coupled with improvements in the management of hyperphosphataemia, led to a reduction in the prevalence of these types of ROD. Since the mid-1990s, there has been an increase in the prevalence of adynamic bone disease as a result of increased suppression of parathyroid hormone through the use of calcium-based phosphate binders and calcitriol therapy. Adynamic bone disease is also associated with several clinical factors, such as older age, use of continuous ambulatory peritoneal dialysis and the presence of diabetes mellitus, as well as the use of calcitriol therapy. Studies of calcium metabolism in patients with CKD have shown that adynamic bone disease is a distinct clinical condition that leads to hypercalcaemia via mechanisms different from that seen in high-turnover bone disease. As high calcium x phosphorus product has been associated with soft tissue and vascular calcifications, and increased mortality, optimizing bone health may be an important way of reducing cardiovascular risk in patients with CKD. To do this, novel, effective, non-calcium, non-aluminium phosphate binders will be necessary.

Effects of Sevelamer Hydrochloride and Calcium Carbonate on Renal Osteodystrophy in Hemodialysis Patients

“…This is consistent with reports of increasing prevalence of ABD in the past two decades, [1][2][3] an increase that has coincided with the widespread use of calcium-based binders combined with more aggressive use of vitamin D analogs. 4,5 Excluding patients with serum phosphorus values Ͼ8.1 mg/dl could not have had a major influence on these results because only two patients were excluded because of such severe hyperphosphatemia.…”

“…Concurrently, there has been an increase in ABD without aluminum toxicity and less MUO. [1][2][3] This has been attributed to greater use of calcium-based phosphate binders, which may result in oversuppression of PTH, especially when used with calcitriol or calcitriol analogues. 4 -6 Calcium-based binder use has also been linked with progression of vascular calcification.…”

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

“…Serum phosphate has been shown to strongly correlate with these cardiovascular events, with emerging evidence that poor bone health may also contribute to phosphate imbalance. (5,7) Individuals with CKD-MBD exhibit a range of renal osteodystrophies with defects ranging from LTO to HTO bone disease. (27,48,49) Classic radiolabel studies performed in the mid-1990s suggest that at either extreme of bone turnover, there is a loss of buffering capacity such that bone cannot accept or retain the increased burden of calcium and presumably phosphate that results from reduced bone mineralization.…”

“…(4) Evidence suggests that vascular disease is at least partially related to poor bone health. (5)(6)(7)(8) Importantly, deviation from the normal range of serum bone biomarkers predicts an increased risk of cardiovascular events, (9) and impaired bone remodeling is associated with increased vascular calcification. (10) In the general population, individuals with osteoporosis have increased atherosclerosis and coronary artery calcification (11)(12)(13)(14) and there is an inverse relationship between coronary artery calcification and bone mineral density (BMD) in both normal and CKD patients.…”

Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy

“…1 These abnormalities encompass a spectrum from severely suppressed to markedly elevated bone turnover. Abnormal bone turnover occurs in approximately 85% of patients with CKD stage 5 on dialysis (CKD-5D), 2 and within this patient group, there is a greater risk of bone fracture than within the general population. [3][4][5] Although turnover abnormalities are well described, 1 little information is available on whether these abnormalities are associated with changes in bone quality.…”